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Antiretroviral Trial Strictures Make Outcomes Harder to Interpret in Clinic: HIV trials need patients with 'major illnesses or more advanced HIV disease'
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48th ICAAC. October 25-28, 2008, Washington, DC
Mark Mascolini
Limiting clinical trials of antiretrovirals to people without major illnesses or more advanced HIV disease "may not provide practitioners with necessary information to translate clinical efficacy [in trials] into effectiveness [in practice] in persons with HIV infection."
A University of Cincinnati team advanced that proposal after comparing short- and long-term responses in 305 people starting their first antiretrovirals in clinical practice and 147 people who took their first antiretrovirals in a clinical trial. Everyone began treatment between 1996 and 2005.
The clinic population began treatment with a significantly lower CD4 count than the trial group (145 versus 265, P < 0.01), and significantly more clinic patients started with fewer than 200 CD4s (58% versus 39%, P < 0.01). But the groups did not differ significantly in pretreatment viral load, or in age, gender, race, or injecting drug use. The groups also had similar rates of prior opportunistic diseases and current diseases.
Trial participants stayed on their first regimen almost twice as long as people seen in the clinic--averaging 25.8 months versus 13.8 months (P < 0.01). While clinic patients missed about 10% of their visits, trial participants missed almost none (P < 0.01). One quarter of clinic patients got admitted to the hospital during follow-up, compared with 12% of trial participants (P < 0.01). Twenty-seven clinic patients (8.85%) died, compared with 5 trial enrollees (3.4%). Among people with a pretreatment CD4 count under 200 or a viral load over 100,000, significantly more clinic patients had an opportunistic infection during follow-up (P < 0.02 for baseline CD4 count and P < 0.01 for baseline viral load).
Despite the initially worse response in the clinic contingent, response rates evened out over the years. Sixty months after starting a first regimen, the two groups had statistically equivalent response rates--45% of trial participants and 50% of clinic patients. And second-line regimens proved equally successful in trials and in the clinic.
The Cincinnati clinicians believe the worse initial response rates in clinic patients than in trial enrollees reflect the more advanced HIV infection in the clinic group. They also suggest that timing of viral load measurements may favor the trial participants, whose loads are measured at predetermined intervals. Clinic patients, on the other hand, often get their viral load measured only when something seems to be going wrong.
"Clinical trials need to include subjects with more severe illness at baseline," the Cincinnati team argued. They also urged trial planners to recruit more under-represented populations.
Reference
1. Forrester JW, Ying J, Coehlo-Prabu N, Fichtenbaum CJ. Differences in clinical efficacy and effectiveness: a comparison of clinical trials to clinical practice. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-1257.
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